Fruit-Derived Extracellular Vesicles Engineered Structural Droplet Drugs for Enhanced Glioblastoma Chemotherapy.

Existing solid nanoparticle-based drug delivery systems remain a great challenge for glioblastoma chemotherapy due to their poor capacities in crossing the blood-brain barrier/blood-brain tumor barrier (BBB/BBTB). Herein, we demonstrated fruit-derived extracellular vesicles (EVs)-engineered structural droplet drugs (ESDD) by programming the self-assembly of fruit-derived EVs at the DOX@squalene-PBS interface, greatly enhancing the antitumor efficacy against glioblastoma. The EVs-engineered structural droplet drugs experience a flexible delivery via deformation-amplified macropinocytosis and membrane fusion, enabling them to highly efficiently cross BBB/BBTB and deeply penetrate glioblastoma tissues. As expected, the EVs-engineered structural droplet drugs exhibited 2.5-fold intracellular uptake, 2.2-fold transcytosis, and 5-fold membrane fusion as higher as the EVs (cRGD modified), allowing the highly efficient accumulation, deep penetration, and cellular internalization into the glioblastoma tissues and thereby significantly extending the survival time of glioblastoma mice. This article is protected by copyright. All rights reserved.